Benzylamine → N-benzyl-2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamide

HRID 2200874Notes

Reaction equation

HRID 2200874 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=3)[C:10]([C:24]([OH:26])=O)=[CH:9][N:8]=1)[CH2:2]2.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1>[CH2:27]([NH:34][C:24]([C:10]1[C:11]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=2)=[N:12][C:7]([N:3]2[CH2:4][CH:5]3[CH:1]([CH2:6]3)[CH2:2]2)=[N:8][CH:9]=1)=[O:26])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 7504BenzylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1176225452-(3-Azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid

Product 1

HCID 73214473N-benzyl-2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In THF (50 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid (16 g, 42.8 mmol), benzylamine (5.0 g, 47 mmol), HATU (17.9 g, 47 mmol) and DIEA (11 g, 85.6 mmol). The reaction mixture was stirred at ambient temperature overnight and concentrated, followed by addition of DCM (500 mL). After the completion of the reaction, water (500 mL×4) was added to the reaction mixture for extraction. The organic phase was concentrated. The crude product was purified by silica gel column chromatography to give N-benzyl-2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-formamide as the product (50 mg, 24% yield).

Workup

  1. concentrationconcentrated
  2. additionfollowed by addition of DCM (500 mL)
  3. customAfter the completion of the reaction, water (500 mL×4)
  4. additionwas added to the reaction mixture for extraction
  5. concentrationThe organic phase was concentrated
  6. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-fd39ec7d80324ff0845654f678eb7da1
Source dataset
uspto-grants-2016_06
Patent number
US09359371B2

Reaction notes

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